Editor, – I would like to offer another explanation for the apparent 'seizure activity' reported by Dr Loadsman (Aust Prescr 2001;24:51-2) when pethidine and tramadol were used concurrently. Both these drugs have serotonin reuptake inhibitor activity and have been implicated in serotonin toxicity when combined with other serotonergic drugs.
Co-administration of pethidine and tramadol could certainly result in a pharmacodynamic interaction, leading to signs and symptoms of excess serotonin in the central nervous system such as 'twitching and anxiety'. These as well as the neuromuscular features, myoclonic spasms, tremor, clonus, hyperreflexia and hypertonia are included in Sternbach's diagnostic criteria for 'serotonin syndrome' and can easily be mistaken for 'seizure activity'. Physicians should be alert to the possibility of serotonin toxicity when pethidine is given to patients who have recently taken, or are still taking, serotonergic drugs (such as selective serotonin reuptake inhibitors and monoamine oxidase inhibitors). Concurrent use of pethidine and tramadol should be undertaken with caution or avoided when possible, because of the risk of serotonin toxicity.
Stephanie Pepper
Drug Information Pharmacist
Hunter Drug Information Service
Newcastle Mater Misericordiae Hospital
Waratah, NSW